Limbic encephalitis: types, symptoms, causes and treatment.

An overview of the characteristics and types of limbic encephalitis, a serious disease.

Limbic encephalitis is a rare medical condition in which various parts of the in which various parts of the limbic brain system become inflamed. The cause behind it may be a tumor or some autoimmune condition, resulting in psychiatric problems in the patient.

This disease has been of considerable interest in recent years because, although there are many neurological diseases that can present psychiatric symptoms, this is the one that goes unnoticed the most and its real diagnosis ends up being made a little late, sometimes misdiagnosing the patient with schizophrenia.

We will now take a closer look at limbic encephalitis, its typologies, most common symptoms, diagnosis and current treatments.

What is limbic encephalitis?

Like all encephalitis, limbic encephalitis is a disease characterized by inflammation of the brain, in this case the parts of the limbic system. a disease characterized by inflammation of the brain, in this case the parts that make up the limbic system.. This disease is usually caused by autoimmunity problems, that is, the organism enters a strange state in which the body produces antibodies against itself, in other words, it attacks itself causing various symptoms, especially in areas such as the hypothalamus and the hippocampus.

Most cases of limbic encephalitis are caused by oncological disease, some type of Cancer that affects the brain in one way or another causing a wide repertoire of psychiatric symptoms. However, it is true that there are some cases in which no tumor is present, the probable cause of limbic encephalitis being an autoimmune disorder or infection.

The disease was first described by J. B. Brierley and coworkers in 1960 by evaluating three cases of this medical condition. The link between limbic encephalitis and cancer was discovered in 1968.Although today it is known that it is not always caused by oncological diseases. In fact, different subtypes of limbic encephalitis are known to exist thanks to the detection of several antibodies involved, including anti-Hu, anti-Ma2 and anti-NMDAR antibodies.

Classification of its types

Depending on whether or not there is a tumor behind its occurrence, we speak of two types of limbic encephalitis: paraneoplastic and non-paraneoplastic. Paraneoplastic limbic encephalitis is one that is caused by some type of cancer or tumor and can be treated by removing and eliminating the tumor cells, while non-paraneoplastic limbic encephalitis is not due to cancer and is usually caused by some type of infection, autoimmune disorder or other unidentified medical condition.

The most common cancers behind paraneoplastic limbic encephalitis are small cell lung cancer, testicular tumors, ovarian teratoma, Hodgkin's lymphoma, and breast cancer. Likewise, within limbic encephalitis we can speak of another classification depending on whether the antibodies that appear in this autoimmune disease attack intracellular antigens or attack surface antigens:

Antibodies to intracellular antigens.

The best known is encephalitis associated with anti-Hu antibodies.associated with small cell lung cancer, which is typical of smokers in their 50s and 60s. Also found in this group is encephalitis associated with anti-Ma, testicular tumors in young people or lung or breast cancer in older adults.

Antibodies to surface antigens

Within this group is potassium channel antibody encephalitis, which is not usually paraneoplastic, although in 20% it is associated with oncologic diseases, especially small cell lung cancer or thymoma. There is also encephalitis mediated by anti-AMPA antibodies, more common in women in their 60s, with lung cancer, breast cancer or thymoma.

Another type of encephalitis of great interest to psychiatry is limbic encephalitis due to antibodies against NMDA receptors or anti-NMDAR encephalitis. This is one of those mediated by antibodies against surface antigens and, although it has been identified relatively recently, it is being concluded that it could be the most frequent, in addition to having a better prognosis than the rest of paraneoplastic encephalitis.

Symptomatology

The symptoms typical of limbic encephalitis, both paraneoplastic and non-paraneoplastic, may appear in a matter of days or weeks. It is considered that the presence of short-term memory deficits is considered to be the hallmark of the disease.However, it happens that in many occasions this sign goes unnoticed or is directly ignored due to the fact that there are many other symptoms also typical of the pathology that call more attention in the psychiatric clinic:

• Headache
• Irritability
• Sleep problems
• Personality changes
• Delusions
• Auditory and visual hallucinations
• Paranoia
• Soliloquies
• Psychomotor agitation
• Seizures
• Catatonia
• Orolingual dyskinesias
• Anomias
• Psychosis
• Affective disorders
• Anxiety
• Obsessive-compulsive symptoms
• Loss of consciousness
• Coma
• Death

It may also happen that the patient's short-term memory is not evaluated because the patient arrives at the consultation sedated, probably after having suffered seizures, psychosis or general agitation. Since it is not possible to administer a memory test to someone who is under the effects of a sedative, this test is often omitted or left for later.

Diagnosis

As we said, despite the fact that its distinctive sign is memory problems, this disease is extremely difficult to diagnose, especially when it is under the influence of a sedative. is extremely difficult to diagnose, especially in its non-paraneoplastic form.. As the rest of the symptoms attract more attention and are of a psychiatric type, it may be thought that what is happening to the patient is that he has a mental disorder rather than a neurological disease, which means that the correct diagnosis takes time to arrive and, in the meantime, the patient is admitted to a psychiatric hospital thinking that he has schizophrenia or another psychotic disorder.

In order to detect limbic encephalitis it is necessary to perform tests that analyze what types of antibodies are in the cerebrospinal fluid and whether the immune system is attacking the organism. Unfortunately this type of testing is not usually done as a routine procedure and tests for some of the autoantibodies involved in the disease are not yet commercially available.

It is also the case that many patients with limbic encephalitis are initially diagnosed with herpesvirus encephalitis. since both the limbic and viral forms share symptoms and since antibody tests are not available, it is often assumed to be caused by herpes simplex.

Treatment

In the case of paraneoplastic limbic encephalitis, treatment generally consists of immunotherapy and removal of the tumor, whenever possible.whenever possible. In this type of encephalitis, recovery will only occur when the tumor has been eliminated.

As for the pharmacological route and also applied to other encephalitis we have intravenous immunoglobulin, plasmapheresis, corticosteroids, cyclophosphamide and rituximab.

Bibliographic references:

• Rodríguez Millán, Julia, Garnica de Cos, Eva, & Malo Ocejo, Pablo. (2014). Psychosis seems, encephalitis is: case of onset with psychiatric symptoms in limbic encephalitis. Journal of the Spanish Association of Neuropsychiatry, 34(122), 375-382. https://dx.doi.org/10.4321/S0211-57352014000200009
• Dalmau J, Tüzün E, Wu H-Y, Masjuan J, Rossi JE, Voloschin A, et al (2007). Paraneoplastic anti-NMDA receptor encephalitis associated with ovarian teratoma. Ann Neurol. 61: 25-36.
• DeAngelis LM, Posner JB (2009). Paraneoplastic syndromes. En: DeAngelis LM, Posner JB, Neurologic complications of cancer, 2ª ed, (577-617). New York: Oxford University Press.
• Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta T, Ascaso C, et al (2001). Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain. 124: 1138-1148.
• Graus F, Saiz A, Dalmau J (2010). Antibodies and neuronal autoimmune disorders of the CNS. J Neurol. 257: 509-517.
• Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J (2000). Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 123: 1481-1494.